Clinical value of neuroimaging indicators of intracranial hypertension in patients with cerebral venous thrombosis.

PURPOSE: Intracranial hypertension (IH) frequently complicates cerebral venous thrombosis (CVT). Distinct neuroimaging findings are associated with IH, yet their discriminative power, reversibility and factors favoring normalization in prospective CVT patients are unknown. We determined test performance measures of neuroimaging signs in acute CVT patients, their longitudinal change under anticoagulation, association with IH at baseline and with recanalization at follow-up. METHODS: We included 26 consecutive acute CVT patients and 26 healthy controls. Patients were classified as having IH based on CSF pressure > 25 cmH2O and/or papilledema on ophthalmological examination or ocular MRI. We assessed optic nerve sheath diameter (ONSD), optic nerve tortuousity, bulbar flattening, lateral and IVth ventricle size, pituitary configuration at baseline and follow-up, and their association with IH and venous recanalization. RESULTS: 46% of CVT patients had IH. ONSD enlargement > 5.8 mm, optic nerve tortuousity and pituitary grade ≥ III had highest sensitivity, ocular bulb flattening and pituitary grade ≥ III highest specificity for IH. Only ONSD reliably discriminated IH at baseline. Recanalization was significantly associated with regressive ONSD and pituitary grade. Other neuroimaging signs tended to regress with recanalization. After treatment, 184.9 ± 44.7 days after diagnosis, bulbar flattening resolved, whereas compared with controls ONSD enlargement (p < 0.001) and partially empty sella (p = 0.017), among other indicators, persisted. CONCLUSION: ONSD and pituitary grading have a high diagnostic value in diagnosing and monitoring CVT-associated IH. Given their limited sensitivity during early CVT and potentially persistent alterations following IH, neuroimaging indicators can neither replace CSF pressure measurement in diagnosing IH, nor determine the duration of anticoagulation.

Artificial Intelligence to Detect Papilledema from Ocular Fundus Photographs.

BACKGROUND: Nonophthalmologist physicians do not confidently perform direct ophthalmoscopy. The use of artificial intelligence to detect papilledema and other optic-disk abnormalities from fundus photographs has not been well studied. METHODS: We trained, validated, and externally tested a deep-learning system to classify optic disks as being normal or having papilledema or other abnormalities from 15,846 retrospectively collected ocular fundus photographs that had been obtained with pharmacologic pupillary dilation and various digital cameras in persons from multiple ethnic populations. Of these photographs, 14,341 from 19 sites in 11 countries were used for training and validation, and 1505 photographs from 5 other sites were used for external testing. Performance at classifying the optic-disk appearance was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity, as compared with a reference standard of clinical diagnoses by neuro-ophthalmologists. RESULTS: The training and validation data sets from 6779 patients included 14,341 photographs: 9156 of normal disks, 2148 of disks with papilledema, and 3037 of disks with other abnormalities. The percentage classified as being normal ranged across sites from 9.8 to 100%; the percentage classified as having papilledema ranged across sites from zero to 59.5%. In the validation set, the system discriminated disks with papilledema from normal disks and disks with nonpapilledema abnormalities with an AUC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) and normal from abnormal disks with an AUC of 0.99 (95% CI, 0.99 to 0.99). In the external-testing data set of 1505 photographs, the system had an AUC for the detection of papilledema of 0.96 (95% CI, 0.95 to 0.97), a sensitivity of 96.4% (95% CI, 93.9 to 98.3), and a specificity of 84.7% (95% CI, 82.3 to 87.1). CONCLUSIONS: A deep-learning system using fundus photographs with pharmacologically dilated pupils differentiated among optic disks with papilledema, normal disks, and disks with nonpapilledema abnormalities. (Funded by the Singapore National Medical Research Council and the SingHealth Duke-NUS Ophthalmology and Visual Sciences Academic Clinical Program.).

Pediatric Cataract Surgery: Rate of Secondary Visual Axis Opacification Depending on Intraocular Lens Type.

PURPOSE: To assess the time course of secondary visual axis opacification (VAO) leading to additional surgery after primary intraocular lens (IOL) implantation in children and to describe further surgical outcomes. Comparison of lens types. DESIGN: Single-center, retrospective analysis of children aged 1 to 14 years who underwent cataract surgery with primary IOL implantation. The surgical technique was either in-bag IOL placement with primary posterior capsulotomy and anterior vitrectomy or bag-in-lens IOL placement. We excluded eyes with visually significant ocular comorbidities. PARTICIPANTS: Total of 135 eyes of 95 children. Of these, 64 had received an acrylic 3-piece IOL, 51 had an acrylic single-piece IOL, and 20 had an acrylic single-piece bag-in-lens IOL. The median ages at surgery were 53 months (interquartile range [IQR], 35-75), 52 months (27-65), and 60 months (40-84) in the 3-piece, 1-piece, and bag-in-lens groups, respectively. METHODS: Analysis of medical records. We used the Kaplan-Meier method and a Cox proportional hazards model with predefined adjustments for age at surgery, year of surgery, and the German Index of Socioeconomic Deprivation (score by postal code) to analyze VAO-free survival by lens type. Patients were invited to attend a clinical visit to achieve longer follow-ups. MAIN OUTCOME MEASURES: The rate of survival without VAO that required clearing of the visual axis after cataract surgery with primary IOL implantation. Any other surgical complications. RESULTS: The overall median follow-up was 19 months (IQR, 3-58). There were 13 cases of VAO, occurring at a median of 10 months (IQR, 10-12) after surgery. Of these, 1 eye had a 3-piece in-bag IOL, 10 eyes had 1-piece in-bag IOLs, and 2 eyes had bag-in-lens IOLs. The adjusted hazard ratio was 32.8 (95% confidence interval [CI], 3.3-327, P = 0.003) for 1-piece acrylic IOLs and 19.6 (CI, 1.22-316, P = 0.036) for bag-in-lens IOLs, compared with 3-piece acrylic in-bag IOLs. Two eyes with bag-in-lens surgery (10%) had an iris capture. There was 1 case of endophthalmitis. We found no cases of postoperative retinal detachment or new glaucoma. CONCLUSIONS: Children with secondary VAO who required a procedure to clear the visual axis generally presented within 15 months. Opacification rates were lowest when a 3-piece acrylic IOL was used.

Thinner temporal peripapillary retinal nerve fibre layer in Stargardt disease detected by optical coherence tomography.

PURPOSE: To evaluate peripapillary retinal nerve fibre layer (RNFL) thickness measured by spectral domain optical coherence tomography (OCT) in patients with Stargardt disease (STGD). METHODS: A cross-sectional, monocentric, observational case-control study. Twenty patients (39 eyes) with ABCA4 mutations graded according to the Fishman STGD classification were included. RNFL measurement was performed using Heidelberg Spectralis SD-OCT. RNFL thickness in STGD patients was compared to age-matched data of healthy individuals provided by the device's manufacturer. A manual readjustment of the optic disc-fovea angle was performed when needed. RESULTS: The mean age at first diagnosis of STGD was 22.9 years (range 9 to 50) and 39.1 years (range 18 to 74) at the time of examination. Thirty-nine percent of eyes (15 eyes) needed manual adjustment of the optic disc-fovea angle due to malfixation of the patients during OCT. The temporal quadrant corresponding to the macula showed a RNFL 16% thinner than controls (mean - 12 µm, 95%CI - 9 to -15 µm). However, global RNFL thickness did not differ from controls due to increased RNFL thickness of 12% in the nasal sectors. Duration and stage of STGD were not correlated to thinner RNFL. CONCLUSION: STGD seems to be associated with thinner peripapillary RNFL in the sector of axons projecting to the degenerated macular area. It is yet unclear as to whether this results from anterograde transneuronal degeneration of direct injury to retinal ganglion cells.

NEGATIVE VESSEL REMODELING IN STARGARDT DISEASE QUANTIFIED WITH VOLUME-RENDERED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To quantify retinal vasculature changes in Stargardt disease1 (STGD1) with volume-rendered optical coherence tomography angiography. METHODS: Optical coherence tomography angiography volumes from healthy subjects and two subgroups of patients with STGD1 with the presence/absence of definitely decreased autofluorescence areas were compared. Optical coherence tomography angiography vessel surface area and vessel volume were measured in central zones (Z) of 1-, 2-, and 3-mm diameter. RESULTS: Twenty nine eyes of 15 patients with STGD1 (20/9 eyes with/without definitely decreased autofluorescence) and 30 eyes of 15 controls contributed data. An enlarged foveal avascular zone was found in patients with STGD1 without and even more with definitely decreased autofluorescence associated with a vessel rarefication in central and also paracentral zones with unnoticeable autofluorescence. Vessel surface area and vessel volume were reduced in both STGD1 subgroups for all zones (P < 0.0001). Stargardt disease 1 eyes when compared to without definitely decreased autofluorescence showed reduced vessel surface area and vessel volume in Z2+3 (both P < 0.05). CONCLUSION: Volume rendering of optical coherence tomography angiography in STGD1 shows a reduced retinal flow in the central macula. This is most likely secondary to loss of neurosensory tissue with disease progression and therefore not likely be favorably influenced by gene transfer and retinal pigment epithelial transplantation. Retinal blood flow assessed by 3D volume-rendered optical coherence tomography angiography could serve as surrogate marker for vascular changes of the central retina.

Side effects of topical atropine 0.05% compared to 0.01% for myopia control in German school children: a pilot study.

PURPOSE: Based on findings of the Asian low-concentration atropine for myopia progression study, a concentration of 0.05% has been proposed as a good compromise between safety and efficacy for myopia control. However, no data on side effects have been published so far in Caucasian children receiving this dose. METHODS: Prior to commencement of bilateral atropine treatment with 0.05% atropine, 19 myopic children aged 5 to 15 years were treated in only one eye at bedtime leaving the other eye as a control. Pupil size, accommodation amplitude and near visual acuity were measured at 10:00 a.m. the next day and compared to the untreated contralateral control eye. The results were then compared to a cohort of 18 children whose treatment with 0.01% atropine commenced in a similar fashion. RESULTS: Twelve children (63%) reported visual impairment or reading difficulties. Anisocoria was 2.9 ± 1.1 mm. In comparison, 0.01% atropine led to a significantly less anisocoria of 0.8 ± 0.7 mm (p < 0.0001). Accommodation was decreased by - 4.2 ± 3.8 D in 0.05% atropine treated eyes, whereas 0.01% atropine induced hypoaccommodation of - 0.05 ± 2.5 D (p < 0.01). Near visual acuity was not significantly reduced in eyes treated with 0.05% atropine compared to 0.01% atropine (p = 0.26). CONCLUSION: Compared to 0.01%, our data indicate stronger more relevant side effects of 0.05% topical atropine in young Caucasian children with progressive myopia as recently reported in Asian children, potentially compromising acceptance and compliance.

Swept-source optical coherence tomography angiography alleviates shadowing artifacts caused by subretinal fluid.

PURPOSE: To characterize the choriocapillaris (CC) structure in relation to subretinal fluid (SRF) as a possible systematic error source using spectral domain (SD-OCTA) compared to swept-source optical coherence tomography angiography (SS-OCTA). METHODS: This is a prospective case-control study of 23 eyes. Ten patients with acute central serous chorioretinopathy (CSC), three patients with partial macular-off retinal detachment (RD) and ten healthy, age-matched controls were included. Abnormal CC decorrelation signals were quantitatively compared in CSC and controls by means of custom image processing. To investigate the influence of SRF on CC OCTA signal, the extent of SRF was quantified with a macular heatmap and compared with the corresponding OCTA signal of the CC. RESULTS: SS-OCTA yielded a more homogeneous OCTA signal from the CC than SD-OCTA, offering less signal dispersion and variability in healthy and diseased eyes. Both devices demonstrated CC signal voids in CSC and RD, respectively. In CCS, the voids were predominantly located in the area with SRF. Compared to SD-OCTA, SS-OCTA delivered a more homogenous OCTA signal and reduced signal voids in the CC underneath SRF in both RD and CSC (CSC, 7.6% ± 6.3% vs, 19.7% ± 9.6%, p < 0.01). Despite this significant attenuation of signal voids, SS-OCTA continued to reveal signal voids below SRF and more pixels with reduced OCTA signals in CSC patients compared to controls (7.6% ± 6.3%, 0.1% ± 0.1%, p < 0.0001). CONCLUSION: Understanding OCTA artifacts is critical to ensure accurate clinical evaluations. In this study, we describe the presence of SRF as an important shadow-causing artifact source for CC OCTA analysis which can be mitigated but not completely eliminated by employing SS-OCTA.

Little effect of 0.01% atropine eye drops as used in myopia prevention on the pattern electroretinogram.

PURPOSE: Daily administration of 0.01% atropine eye drops is a promising approach for myopia control. The mechanism of action is believed to involve the dopaminergic system of the retina, triggering an increased release of dopamine. Previous studies in psychiatric condition such as major depression suggest that pattern electroretinogram (PERG) amplitudes are modulated by changes in retinal dopamine. It is thus plausible that atropine eye drops could have an effect on PERG amplitudes. The present study was designed to test this, assessing the difference in amplitude between contrast levels and the ratio of amplitudes between check sizes as primary endpoints. METHODS: We included 14 participants with no more than ± 2 diopters of ametropia and visual acuity of at least 1.0. One eye was chosen randomly in each participant for atropine application (14 days, one drop of 0.01% atropine solution once daily before bedtime). We recorded two sets of steady-state PERG recordings: one with different contrasts (25% and 98%) and one with different check sizes (0.8° and 17°). Near-point distance, near visual acuity, and pupil diameter were measured additionally. RESULTS: The recordings to different contrasts did not show atropine-related changes of PERG amplitude. A small increase by 6% of the amplitude difference between contrast levels with atropine application was not significant (p = 0.08). Raw amplitudes in the check size condition increased with atropine by 17% (p < 0.01) and 10% (p < 0.03) for small and large checks, respectively, without a significant concomitant effect on the amplitude ratio. Pupil size was significantly affected (median increase 0.5 mm, p < 0.002). However, neither of the experimental conditions was associated with a significant correlation between pupil size and PERG effects. CONCLUSION: The effects on PERG primary endpoints after the 14-day period of atropine administration were small, especially compared to effect sizes in major depression, and statistically insignificant. Effects on raw amplitude were inconsistent. The present results suggest that retinal processing as reflected by PERG does not sizably change following a treatment regimen with atropine that is typical for myopia control.

[Non-arteritic Anterior Ischaemic Optic Neuropathy: Pathogenesis and Therapeutic Approaches]. / Pathogenese und Therapie der nicht arteriitischen anterioren ischämischen Optikusneuropathie.

Non-arteritic anterior ischemic optic neuropathy (NAION) is an acute neurodegenerative disease with a largely elusive early pathogenesis and no specific therapy. Recent data from animal models of the disease as well as from epidemiological studies have provided new insights into the disease mechanism of NAION. On the basis of this new knowledge, a broad variety of therapeutic approaches is currently being evaluated in animal and clinical studies. This review aims to provide an overview of the pathogenesis as well as neuroprotective therapeutic concepts of recent and currently running studies.

Sirolimus-induced regression of a large orbital lymphangioma.

Microcystic lymphatic malformations are difficult to treat surgically, especially when located in the orbital apex. Recently, pharmacologic inhibition of the mTOR pathway by sirolimus was reported as a safe and efficacious treatment option for lymphatic malformations (also known as lymphangiomas). We report the case of a young male patient in which a unilateral, retrobulbar lymphatic malformation regressed to a large extent under treatment with 1 mg sirolimus given orally twice a day over a period of six months.

[Amblyopia and refractive error]. / Update Augenheilkunde ­ Amblyopie und Refraktionsfehler.

Myopia is on the increase worldwide and will become a major challenge over the next decades in terms of secondary ophthalmologic complications. There are effective therapeutic options available to slow or prevent the progression of myopia. So far, it has not been investigated whether there are possible additive effects of these interventions. Further investigations - especially in Caucasian populations - are necessary to verify the study results available from Asia. There is limited data on how long further progression of myopia is preventable. A therapy appears reasonable as long as a progression of myopia is detectable.Consistent childhood amblyopia screening provides a cost-effective measure for the prevention of visual disturbances over the course of life. How this can be best integrated into the existing system of "U-investigations", must be clarified by the cost-bearers and professional associations. This discourse should be supported by close interdisciplinary exchange and further studies on the prevalence of different degrees of amblyopia. In addition, sensitive and specific or even multi-stage tests should be developed in order to implement an early detection that is cost-effective and saves resources.

International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON.

Argon mediates protection by interleukin-8 suppression via a TLR2/TLR4/STAT3/NF-κB pathway in a model of apoptosis in neuroblastoma cells in vitro and following ischemia-reperfusion injury in rat retina in vivo.

Argon has recently come into scientific focus as a neuroprotective agent. The underlying neuroprotective mechanism remains unknown although toll-like receptors were recently suggested to play an important role. We hypothesized that TLR-associated downstream transcription factors are responsible for argon's effects, leading to anti-apoptotic and anti-inflammatory properties. Apoptosis was induced in human neuroblastoma cells. Immediately afterwards, argon treatment (75 Vol% for 2 h) was initiated. Cells were analyzed, measuring mitochondrial membrane potential, reactive-oxygen-species, annexin-V/propidium iodide staining, transcription factor phosphorylation and binding activity as well as protein and mRNA expression of interleukins. Argon's in vivo effects were analyzed by quantification of retinal ganglion cell density, mRNA expression, serum cytokine analysis and immunohistochemistry after retinal ischemia reperfusion injury (IRI) in rats. Argon diminished rotenone-induced kappa-light-chain-enhancer' of activated B-cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) but not STAT5 or cAMP-response element-binding protein (CREB) phosphorylation and DNA-binding activity. Argon treatment attenuated apoptosis by preservation of mitochondrial membrane potential and decline in reactive oxygen species (ROS) generation. NF-κB and STAT3 inhibition, as well as TLR2 and TLR4 inhibition reversed argon's effects on IL-8 mRNA expression. Argon attenuated rotenone-induced IL-8 protein and mRNA expression in vitro. Inhibition of TLR2 and 4 attenuated argon's protective effect in vivo reducing IRI driven retinal IL-8 expression. IL-8 expression was found in the retina in co-localization with Müller cells and retinal ganglion cells. Argon mediates its neuroprotective effects by TLR-mediated regulation of transcription factors NF-κB and STAT3, thus decreasing interleukin-8 expression in vitro and in vivo. These findings may open up new opportunities to effectively treat cerebral ischemia and reperfusion injury through the inhalation of argon. Argon exerts its protective effects in vitro and in vivo via toll-like receptors TLR2 and TLR4 signaling, followed by alteration of downstream enzymes. In conclusion, argon mediates its beneficial effects by suppression of STAT3 and NF-κB phosphorylation and subsequent suppression of interleukin IL-8 protein expression. These novel findings may open up opportunities for argon as a therapeutic agent, particularly in the treatment of neuronal injury. Cover image for this issue: doi: 10.1111/jnc.13334.

VEGF-A165b is an endogenous neuroprotective splice isoform of vascular endothelial growth factor A in vivo and in vitro.

Vascular endothelial growth factor (VEGF) A is generated as two isoform families by alternative RNA splicing, represented by VEGF-A165a and VEGF-A165b. These isoforms have opposing actions on vascular permeability, angiogenesis, and vasodilatation. The proangiogenic VEGF-A165a isoform is neuroprotective in hippocampal, dorsal root ganglia, and retinal neurons, but its propermeability, vasodilatatory, and angiogenic properties limit its therapeutic usefulness. In contrast, a neuroprotective effect of endogenous VEGF-A165b on neurons would be advantageous for neurodegenerative pathologies. Endogenous expression of human and rat VEGF-A165b was detected in hippocampal and cortical neurons. VEGF-A165b formed a significant proportion of total VEGF-A in rat brain. Recombinant human VEGF-A165b exerted neuroprotective effects in response to multiple insults, including glutamatergic excitotoxicity in hippocampal neurons, chemotherapy-induced cytotoxicity of dorsal root ganglion neurons, and retinal ganglion cells (RGCs) in rat retinal ischemia-reperfusion injury in vivo. Neuroprotection was dependent on VEGFR2 and MEK1/2 activation but not on p38 or phosphatidylinositol 3-kinase activation. Recombinant human VEGF-A165b is a neuroprotective agent that effectively protects both peripheral and central neurons in vivo and in vitro through VEGFR2, MEK1/2, and inhibition of caspase-3 induction. VEGF-A165b may be therapeutically useful for pathologies that involve neuronal damage, including hippocampal neurodegeneration, glaucoma diabetic retinopathy, and peripheral neuropathy. The endogenous nature of VEGF-A165b expression suggests that non-isoform-specific inhibition of VEGF-A (for antiangiogenic reasons) may be damaging to retinal and sensory neurons.

The Freiburg Acuity Test in Preschool Children: Testability, Test-Retest Variability, and Comparison With LEA Symbols.

Purpose: To determine the testability, performance, and test-retest variability (TRV) of visual acuity (VA) assessment using the Freiburg Visual Acuity Test (FrACT) compared to the LEA Symbols Test (LEA) in preschool children. Methods: In 134 preschool children aged 3.0 to 6.8 years, monocular VA of each eye was measured twice with a four-orientation Landolt C version of the FrACT and once with the LEA. FrACT runs were preceded by a binocular run for explanatory purposes. Test order alternated between subjects. Optotypes were presented on a computer monitor (FrACT) or on cards (LEA) at a distance of 3 m. Results: Overall, 68% completed the FrACT (91/134 children) and 88% completed the LEA (118/134 children). Testability depended on age: FrACT, 19% (<4 years) and 87% (≥4 years); LEA, 70% (<4 years) and 95% (≥4 years). Mean ± SD VA difference between tests was 0.11 ± 0.19 logarithm of the minimum angle of resolution [logMAR], with LEA reporting better acuity. The difference depended on age (0.27 ± 0.23 logMAR [<4 years], 0.09 ± 0.18 logMAR [≥4 years], P < 0.001) and on test sequence (higher age dependence of FrACT VAs for LEA first, P < 0.001). The 95% limits of agreement for the FrACT TRV were ±0.298 logMAR. Conclusions: The examiner-independent FrACT, using international reference Landolt C optotypes, can be used to assess VA in preschool children aged ≥4 years, with reliability comparable to other pediatric VA tests. Translational Relevance: Use of the automated FrACT for VA assessment in preschool children may benefit objectivity and validity as it is a computerized test and employs the international reference Landolt C optotype.

Disease Course of Clinically Isolated Optic Neuritis.

BACKGROUND AND OBJECTIVES: Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of visual pathway neuroprotection trials. METHODS: This is a secondary analysis of longitudinal data from the TONE trial, which included 103 patients from 12 German academic tertiary centers with acute unilateral optic neuritis as a clinically isolated syndrome and baseline high-contrast visual acuity <0.5 decimal. Patients were randomized to 1,000 mg methylprednisolone i.v./d plus either erythropoietin (33,000 IU/d) or placebo (saline solution) for 3 days. They were followed up at standardized intervals with a battery of tests including high-contrast visual acuity, low-contrast letter acuity, contrast sensitivity, visual fields, visual evoked potentials, and retinal optical coherence tomography. At 6 months, participants answered a standardized questionnaire on vision-related quality of life (NEI-VFQ 25). We describe the disease course with mixed-effects piecewise linear models and calculate structure-function correlations using Pearson r. Because erythropoietin had no effect on the visual system, we use pooled (treatment-agnostic) data. RESULTS: Patients experienced initial rapid and then decelerating improvements of visual function with thinning of inner and thickening of outer retinal layers. At 6 months, visual parameters were positively correlated with inner and negatively correlated with outer retinal thickness changes. Peripapillary retinal nerve fiber layer thinning predominantly occurred in sectors without previous swelling. At 6 months, macular ganglion cell and inner plexiform layer thinning was weakly correlated with the P100 peak time (r = -0.11) and moderately correlated with the amplitude of visual evoked potentials (r = 0.35). Only functional outcomes were at least moderately correlated with vision-related quality of life. DISCUSSION: The longitudinal data from this large study cohort may serve as a reference for the clinical course of acute optic neuritis. The pattern of correlation between visual evoked potentials and inner retinal thinning may argue that the latter is mostly due to ganglion cell loss, rather than dysfunction. Visual pathway neuroprotection trials with functional outcomes are needed to confirm that candidate drugs will benefit patients' vision-related quality of life. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov, NCT01962571.